It is well established that interaction of fibrinogen with specific receptors associated with the glycoprotein IIb-IIIa (GPIIb-GPIIIa) complex is essential for platelet aggregation. Unstimulated platelets do not bind fibrinogen, and therefore do not aggregate in the circulation. When platelets are stimulated by agonists such as ADP, epinephrine, thrombin, or prostaglandin endoperoxides, fibrinogen receptors associated with the GPIIb-GPIIIa complex become exposed on the platelet surface, resulting in fibrinogen binding and subsequent platelet aggregation. The common interpretation is that ADP is an essential mediator of fibrinogen receptor exposure under physiological conditions. Evidence suggests that during tissue injury, ADP is formed in sufficient quantities to cause platelet aggregation.
Ouyang, C. and Huang, T., Biochim. Biophys. Acta 757:332-341 (1983) and Thrombos. Res. 33:125-138 (1984) report a crude preparation of a platelet aggregation inhibiting substance from Trimeresurus gramineus snake venom. The material was described as an acidic phospholipase A rich in aspartic acid, glutamic acid and cysteine, isolated by ion exchange chromatography and gel filtration. Ouyang et al. identified a single 12.4 kd band in the preparation by SDS-polyacrylamide gel electrophoresis and disc electrophoresis. They reported an estimated minimal molecular weight of 11,682 based upon 109 amino acid residues.
Despite the potency of the Ouyang et al. factor, the phospholipase A activity of the material renders it wholly unsuitable for clinical use owing to the hemolytic effect of phospholipase A on erythrocytes. Moreover, the impure material may contain one or more contaminating toxins from the raw snake venom. It is known that certain toxins found in snake venoms are toxic to humans in nanogram amounts.